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A total of Of these, Thus Colorectal cancer screening in the control arm contamination was assessed by a questionnaire in a small sample of participants. The rate was estimated as In addition, the rate of colonoscopy after the screening phase was estimated as The primary endpoint was colorectal cancer mortality, with colorectal cancer incidence a key secondary endpoint.

All cancers and deaths were ascertained primarily by means of an annual questionnaire. Median follow-up time was The incidence rate of colorectal cancer was The absolute colorectal cancer risk reduction was 0. In the distal colon the RR was. The colorectal cancer mortality rate was 2. The absolute reduction in risk of colorectal cancer death was 0.

The mortality RR for the distal colon was 0. Treatment of diagnosed colorectal cancers was very similar by arm within each stage. The rate of bowel perforations was 2. The RR for deaths from all causes excluding prostate, lung, colorectal, and ovarian cancers was 0. There are no strong direct data to determine frequency of screening tests in programs of screening. Sigmoidoscopy detects lesions in the left colon directly but detects lesions in the right colon only indirectly when a positive sigmoidoscopy that may variously be defined as a finding of advanced adenoma, any adenoma, or any polyp is used to trigger a colonoscopic examination of the whole colon.

It was estimated that combined screening with one-time FOBT and sigmoidoscopy would detect Examination of the rectum and sigmoid colon during colonoscopy was defined as a surrogate for sigmoidoscopy. This represented a small but statistically insignificant increase in the rate of detection of advanced neoplasia when compared with FS alone The latter result could be achieved assuming that all patients with an adenoma in the distal colon undergo complete colonoscopy. FIT alone resulted in a sensitivity of FIT plus the finding of advanced neoplasia in the rectosigmoid colon yielded a sensitivity of Thus, in this trial, the addition of sigmoidoscopy to FIT did not substantially improve the detection of right-sided colon cancers, compared with FIT alone.

Forty-one cases of CRC were detected 0. In patients who have undergone colonoscopic polypectomy, colonoscopic examination is a more sensitive method of surveillance than double-contrast barium enema. Most indirect evidence is about detection rate of lesions that may be clinically important like early CRC or advanced adenomas.

Some casecontrol results are available. One RCT of colonoscopy has been initiated. One-half of those with advanced proximal neoplasia, however, had no distal adenomas. In a study of 1, adults aged 50 years or older who underwent colonoscopic screening as part of a program sponsored by an employer, 5. If colonoscopic screening is performed only in patients with distal polyps, about half the cases of advanced proximal neoplasia will not be detected.

A study of colonoscopy in women compared the yield of sigmoidoscopy versus colonoscopy. Among 1, women, cancer was found in one woman and advanced colonic neoplasia in 72 women or 4. The authors focused, however, on RR i. In addition, the natural history of advanced neoplasia is not known, so its importance as an outcome in studies of detection is not clear.

The predominant age range of participants was 50 to 66 years. Of the 43, participants aged 50 to 66 years, advanced neoplasia was detected in 5. Clinically significant complications requiring medical intervention were rare 0. There were no deaths; however, the author reported that collection of day complications data was not systematic therefore, the data may not be reliable. Detection rates among gastroenterologists mean number of lesions per patient screened, 0.

Examiners whose mean withdrawal time was 6 minutes or more had higher detection rates than those with mean withdrawal times of less than 6 minutes While the phenomenon of flat neoplasms has been appreciated for years in Japan, it has more recently been described in the United States. At the same time, the existence of very flat or depressed lesions depressed lesions are very uncommon but are highly likely to contain cancer means that endoscopists will want to pay increasing attention to this problem.

The term serrated polyp is currently used to include hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, and mixed serrated polyps. However, the histologic and molecular characteristics of some serrated lesions suggest possibly important malignant potential mutations in the BRAF gene may be an early step toward carcinogenesis in serrated polyps. In , authors of one study reported variability of detection rates for proximal serrated polyps.

They studied 15 colonoscopists on faculty at one university and showed, during the years to , a wide variation in detection rate for proximal serrated polyps, ranging per colonoscopy from 0. Based on case-control data about sigmoidoscopy, noted above, it has been speculated in the past that protection for the right colon might be similar to that found for the left colon. However, a recent case-control study of colonoscopy raises questions about whether the impact of colonoscopy on right-sided lesions might be different than the impact on left-sided lesions.

Controls were selected from persons who did not die of CRC. Billing claims were used to assess exposure to previous colonoscopy. The OR for the association between complete colonoscopy and left-sided lesions was 0. For right-sided lesions, however, the OR of 0. It is possible that poor prep or incomplete mucosal inspection caused important lesions to be missed. It is also possible that examination was complete but some right-sided lesions simply grow rapidly and are not detected and treated by periodic colonoscopy. In other words, it is impossible to determine the reason for the dramatically different results on the right side compared to the left side, which are either the result of physician-related or patient-related factors or are the result of the biology of cancer.

In a population-based study from Germany, data were obtained from administrative records and medical records; 1, case patients with CRC were compared with 1, participants without CRC , aged 50 years or older. While this study does not assess CRC mortality, the results suggest that the magnitude of the right side versus the left side difference may be smaller than previously found. These images simulate the effect of a conventional colonoscopy. Patients must take laxatives to clean the colon before the procedure, and the colon is insufflated with air sometimes carbon dioxide by insertion of a rectal tube just prior to radiographic examination.

Unknowns from the study include the following for either OC or CTC: the number of detected polyps that would have progressed to invasive cancer, and the number of people harmed by the screening process. This study suggests that virtual colonoscopy might be an acceptable screening or surveillance test for persons with a high risk of CRC, but this cross-sectional study does not address outcome or frequency of testing in high-risk persons.

Some studies have assessed how well virtual colonoscopy can detect colorectal polyps without a laxative prep. The question is of great importance for implementation because the laxative prep required by both conventional colonoscopy and virtual colonoscopy is considered a great disadvantage by patients. Another study 73 utilized low fiber diet, orally ingested contrast, and electronic cleansing , a process that subtracts tagged feces. This study shows that CTC without a laxative prep detects small 1 cm lesions with high sensitivity and is acceptable to patients.

Long-term utilization of CTC will depend on several issues including the frequency of follow-up exams that would be needed to detect smaller lesions that were undetected and may grow over time. Extracolonic abnormalities are common in CT colonography. CT colonography was performed immediately prior to colonoscopy and these findings required further evaluation. It is unstated to what extent the follow-up of these incidental findings benefited patients. Suspected abnormalities involved kidney 34 , chest 22 , liver 8 , ovary 6 , renal or splenic arteries 4 , retroperitoneum 3 , and pancreas 1 ; 76 however, the extent to which these findings will contribute to benefits or harms is uncertain.

The larger study 77 found that 8. Both of these estimates of cost are higher than previous studies have found. The extent to which any patients benefited from the detection of extracolonic findings is not clear. Because both of these studies were conducted in academic medical centers, the generalizability to other settings is also not clear. Neither of these studies examined the effect of extracolonic findings on patient anxiety and psychological function. While specificity for detection of polyps is homogeneously high in many studies, sensitivity can vary widely. These variations are attributable to a number of factors including characteristics of the CT scanner and detector, width of collimation, mode of imaging two dimensional [2-D] vs.

Conducted in a blinded way with prestated hypotheses and analyses, the study found that among 4, patients, the DNA panel had a sensitivity for CRC of On this basis, the approach looks promising but would be improved, if possible, by increased sensitivity perhaps by increasing the number of DNA markers and by reduced cost. Lindholm E, Brevinge H, Haglind E: Survival benefit in a randomized clinical trial of faecal occult blood screening for colorectal cancer. Br J Surg 95 8 : , Results for first , subjects. Lancet 1 : , A prospective randomized study at Funen in Denmark. Scand J Gastroenterol 22 6 : , A prospective randomized study at Funen, Denmark.

Scand J Gastroenterol 24 5 : , Minnesota Colon Cancer Control Study. N Engl J Med 19 : , J Natl Cancer Inst 91 5 : , Is mortality reduced by chance selection for screening colonoscopy? JAMA 13 : , J Natl Cancer Inst 89 19 : , N Engl J Med 22 : , Lancet : , Gut 45 4 : , Gut 50 6 : , Gut 61 7 : , Gut 50 1 : , Scand J Gastroenterol 39 9 : , Moayyedi P, Achkar E: Does fecal occult blood testing really reduce mortality?

A reanalysis of systematic review data. Am J Gastroenterol 2 : , Health Econ 7 1 : , Comput Biomed Res 32 1 : , London, England: WB Saunders, , pp Suggested technique for fecal occult blood testing and interpretation in colorectal cancer screening. American College of Physicians. Ann Intern Med 10 : , Am J Gastroenterol 6 : , Eddy DM: Screening for colorectal cancer. Ann Intern Med 5 : , Long-term follow-up in a large group practice setting. A controlled trial of fecal occult blood testing in 27, subjects.

Cancer 62 3 : , What is the best strategy for colorectal cancer screening? Br J Cancer 2 : , Ann Intern Med 4 : , Gastroenterology 2 : , Preventive Services Task Force. Ann Intern Med 9 : , Curr Oncol Rep 8 6 : , J Med Screen 14 3 : , Br J Cancer 8 : , JAMA 22 : , Front Gastrointest Res , N Engl J Med 1 : , JAMA 17 : , JAMA 9 : , BMJ b, Telemark Polyp Study I. Scand J Gastroenterol 34 4 : , Gastroenterology 93 5 : , Ann Intern Med 1 : , J Natl Cancer Inst 2 : , J Natl Cancer Inst 17 : , N Engl J Med 25 : , N Engl J Med 10 : , J Natl Cancer Inst 84 20 : , N Engl J Med 8 : , Clin Gastroenterol Hepatol 7 12 : , Scand J Gastroenterol 38 6 : , National Polyp Study Work Group.

N Engl J Med 24 : , Veterans Affairs Cooperative Study Group N Engl J Med 3 : , N Engl J Med 20 : , N Engl J Med 18 : , Lieberman D: Nonpolypoid colorectal neoplasia in the United States: the parachute is open. Gastroenterology 1 : , Clin Gastroenterol Hepatol 9 1 : , Am J Clin Pathol 3 : , Ransohoff DF: How much does colonoscopy reduce colon cancer mortality?

Smith MJ: Colon cancer screening hitting its stride but obstacles impairs reaching final goal. Gastroenterology and Endoscopy News 59 3 : 9, Ferrucci JT: Colon cancer screening with virtual colonoscopy: promise, polyps, politics. N Engl J Med 12 : , JAMA 23 : , Gastroenterology 5 : , Am J Gastroenterol 96 10 : , Gastroenterology 4 : , Radiology 1 : , J Gen Intern Med 24 1 : , Ann Intern Med 8 : , Am J Epidemiol 9 : , Cell 87 2 : , J Natl Cancer Inst 93 11 : , N Engl J Med 5 : , N Engl J Med 26 : , Woolf SH: A smarter strategy? Reflections on fecal DNA screening for colorectal cancer.

Despite a series of incremental changes in health system organization, the general trend towards decentralization of the purchasing agent has been an unmistakable phenomenon. In many instances the strategic movement of the purchasing function to more localized settings, has been used to consolidate a heightened sense of financial accountability and encourage local autonomy.

Such changes in health-system organization have important implications with regard to the local purchaser ability to cater to specific population health need. Given that such arrangements have a tendency to encourage risk segmentation, resource allocation mechanisms are important when responding to population need. In this context, this chapter examines how disease burden across Europe and Australia guides resource allocation mechanisms. The chapter focuses primarily on how CRC influences resource allocation mechanisms across the study countries and is split into two main sections: the first, assesses the current burden of CRC across Europe and Australia, introduces CRC epidemiological trends, primarily around traditional indicators such as incidence, mortality and survival, and examines variations in disease burden over the last decade.

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The second section examines how resources are allocated at various stages of the CRC management pathway, assesses the current context for CRC funding, by identifying explicit forms of diseaserelated resource allocation, and examines how various aspects of management influence funding mechanisms. As a proportion of European cancer incidence, Age Standardised Rate measuring number of cases per , population. There are noted differences between European countries for incidence and mortality. There have been a number of hypotheses for this pattern. It may reflect greater fruit, vegetable, fiber and fish consumption and more active lifestyles in the south than elsewhere; while poorer prognosis in the east may reflect poorer treatment and advanced stage at diagnosis.

There may also be genetic differences across Europe thereby creating lower proportions of high risk individuals in the south than north. There may be a number of factors accounting for this gender difference. There may be inherent biological differences in women providing added protection against CRC, such as hormonal or genetic factors. There may also be lifestyle difference between the sexes such as greater fruit and vegetable consumption in women than men, a hypothesis supported by the finding of greater plasma carotenoids in women than men in across Europe.

When examined in comparison with other cancers with high incidence in Europe, CRC does not fare 30 as well. In comparison the latest European 5 year relative survival for breast cancer is In the majority of countries survival is better for women than men. Again there appears to be regional differences in survival, with poor CRC survival particularly in Eastern Europe. The latest data, however, no longer supports this trend for all Northern European countries, except for the UK and Denmark.

Europe overall has improved survival by 4. There are a number of hypotheses to explain these differences between countries. Early detection appears to be a significant predictor for survival, and correcting for stage at diagnosis shrinks country differences somewhat. Additional factors affecting survival between countries are proportion of adenocarcinomas in polyps less are associated with improved prognosis , higher proportion of tumours not microscopically verified, and access to curative surgery. Furthermore, treatment for CRC has also improved with the advent of better surgery, radiotherapy and combination chemotherapy.

Source: Berrino F, et al, France has been consistently one of the better performing countries for CRC survival. Only Denmark fares worse for Northern and Southern European countries. This ranking has not improved with time, although there have been marked improvements since survival data begun collecting.

Survival of curative resection in all stages has increased since in the UK, due to downstaging of the disease earlier detection , improved diagnostic staging, and improvements in treatment and peri-operative care. Furthermore mechanisms of formal resource allocation were mainly seen to be prospective. In the UK, semi-autonomous primary care trusts PCTs were allocated funds based on a set of proxy indicators used to define local population need.

These were based on a series of demographic and socio-economic indicators, in addition to the current status disease burden at the local level. On the other hand in the Australian public healthcare-system which uses a publicprivate financing money was allocated from the federal to the state governments on the basis of a fiveyear Australian Healthcare Agreement.

The money is then used to fund public hospital health services within the area. Countries that used social health insurance as a main method of financing healthcare were found to lack formal methods of resource allocation. Use of social health funds as the main collector of revenue, the locus of financial pooling as well as the purchaser of care, meant that there was an acute lack of financial distribution in the form of prospective budgeting in western and central Eastern Europe. Out of the nine countries that reported no formal resource allocation, five used social health insurance systems as the main method of finance France, Hungary, Turkey, Slovakia and Germany.

In all instances, the main form of financial allocation took place between the purchaser of care and provider of care. In Germany, statutory care in the form of medical services was reimbursed using a DRG payment system. In addition, in Hungary a system of payment based on the American DRGs and the German fee-for-service points system was used to finance out and inpatient care.

In all of these countries, central government played a critical role in sanctioning the reimbursement of services and thus coordinating the rationing of care. Healy, Sharman and Lonkuge, indicate that the Ministry of Health plays a significant role in the coordination of expenditure. In Germany this occurred by way of the Federal Joint Committee. Placed at a national level, this organization has the responsibility of defining the scope of reimbursement within ambulatory care.

Despite informal resource allocation characterized by retrospective payment type, certain forms of prospective budget allocation were also seen as informal. In these settings budgets were based on various transitory arrangements. The Russian health care system is based on many sources of revenue that are collected from federal, regional and local taxes, as well as social health insurance contributions.

In the Russian case, funds from specific revenue sources are designated to specific hospital services, and therefore play an essential part framing patient care. However, in this setting, there is no clear and transparent mechanism for defining how much money should be allocated to which services. This creates problems as to which services should be provided for free and which should be paid for out of pocket.

The use of a complex allocation mechanism was a clear phenomenon with the majority of European countries and Australia which used a hybrid system of allocation to distribute funds at the national, regional and local level. These levels of distribution were found to arise from historical issues surrounding regional autonomy or, in some cases, functions of recently.

جس نے ہڑتال کرنی ہے کر لے، صحت پر کوئی سمجھوتہ نہیں ہوگا:چیف جسٹس - PAKasia

Given the significant degree of regional autonomy in Spain and Italy, resource allocation from the federal to the state level played a significant part in determining region-specific budgets. In Denmark, on the other hand, revenue collection and the subsequent pooling of funds occurring at the regional level has caused there to be a series of risk equalization mechanisms, to avoid risk segmentation.

Essentially taxes levied at the national level are reallocated based on risk. However in the UK, the relatively recent split between the purchaser and provider has lead to a series of interesting allocation processes. In the majority of cases, resource mobilization between the two organization is based on a complex array of globalised budgets defined by historical analysis of past use , service lead agreements based on cost and value agreements made between the two parties and targeted payment by results PbR.

Finally, risk equalization mechanisms, in their own right, seemed to play a prominent part in the overall amount of money allocated to purchasers of care. This was seen mostly within countries that presented social health insurance schemes as the main mode of healthcare finance. Indeed, this was the main way that such countries tried to safeguard against risk-segmentation.

A prime example of this was seen within the Netherlands where the purchasers of care were seen to adjust budgets based on the risk profile of the specified population.

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Formulas used for reallocation were based on age, sex, socioeconomic deprivation, sources of income, and socioeconomic status. Equalization formulas also took into account measures of disease burden. This was seen in the form the creation of specific cost-groups for expensive drugs and DRG coding for chronic disease. These indicators were used to distribute funds accordingly; at the beginning and end of the year. Allocation specifically to cancer was found to be extremely limited, with disease specific allocation only in Denmark, the Russian Federation, Romania, Australia and the UK.

Across the 18 countries studied, Australia was the only country to report the use of the explicit allocation process for all cancers. Denmark, the Netherlands, Romania and the UK only reported explicit mechanisms of resource allocation to cancer. Yet closer analysis of these methods of resource distribution found significant differences with regard to the distribution of funds.


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In the UK money allocated to cancer was given on a yearly basis. However, in the Russian Federation oncology care is not covered by medical insurance and is exclusively funded by federal and regional budgets. Given that the majority of care is given in specialist institutions, in most cases resources were allocated on a per diem basis, with some additional cost for the consultation time. These arrangements created significant issues relating to underfunding. Particular forms of treatment tended to be financed using cost estimations.

However, given that these values were defined without transparent and clear mechanisms, the costs of treatment in real terms often exceeded proposed estimates. Many respondents indicated that the resources allocated to cancer in general and CRC in particular, were insufficient, although in the majority of cases no appropriate measure of need versus expenditure was available to substantiate this claim, but gaps in specific parts of the care delivery pattern were mentioned.

While countries such as the UK cited the recent levels of increased investment in cancer overall as the reasoning behind this opinion, the majority of countries highlighted lack of facilities, shortage in the clinical skill-set and poor access to pharmaceuticals, as the reasoning behind this negative response. More specifically, delays in the inclusion of important novel drugs on the Hungarian reimbursement list placed inherent barriers to pharmaceutical access.

Furthermore, long diagnosis and treatment waiting times,. In countries with poorer cancer registry data collection quality Hungary, Slovakia, Russia these numbers may be less accurate, however, for the remaining countries this adjustment helps estimate the cancer spending per cancer patient.

The total cancer spending per total cancer incidence and mortality shows large variations between countries. The highest spending countries appear to be France, Germany and Sweden, while the lowest spending countries appear to be Russia and the Netherlands. For colorectal cancer spending adjusted for colorectal cancer burden, the highest spending countries appear to be France, Germany and the Netherlands, while the lowest appear to be Hungary and Spain. Furthermore, programmes within these countries were found to be at different stages of development.

In terms of years in operation, Slovakia presented one of the more established programmes, with CRC screening being part of a legislated reimbursement package since Under Act No. In the UK, however, the national screening programme is still in the early stages of implementation, with CRC screening roll-out currently taking place between the years of and The majority of the remaining countries were still within the pilot stage Denmark, Germany, Hungary the Netherlands, Romania, Spain and Sweden.

Unlike CRC, the existence of national breast cancer screening programmes seems to be more widespread. Greece and Portugal were the only countries to have no national or pilot breast screening programme. Finally, Slovakia and Poland are the only countries in which national programmes for prostate screening are run. Explicit allocation of resources to adult screening seemed to be standard within countries offering such programmes.

Kepler8 en Espanol. Pulsa cualquiera de los 12 iconos que rodean al personaje del siguiente grabado. Dos signos de agua que se acercan por su sensibilidad. Responder Cancelar respuesta. Y es que el sentimiento del amor, constituye una parte fundamental en la vida y la felicidad de los individuos. Esperanza Gracia. Madeleine16 Miembro de plata Soy compatible con los cancer, aries y tauro. Los cancerianos de hecho expresan demasiado afecto y demandas por parte de la. Sobre los Aries. Significant differences in Raman intensities of prominent SERS bands were observed between normal and cancer tissues.

This exploratory study demonstrated great potential for developing label-free tissue SERS analysis into a clinical tool for esophageal cancer detection. Increased lipoprotein lipase activity in non-small cell lung cancer tissue predicts shorter patient survival. Cumulative evidence suggests the involvement of lipoprotein lipase LPL in tumor progression. We tested the hypothesis that increased LPL activity in resectable non-small cell lung cancer NSCLC tissue and the increased LPL gene expression in the surrounding non- cancer lung tissue found in our previous study are predictors of patient survival.

Paired samples of lung cancer tissue and adjacent non- cancer lung tissue were collected from resected specimens for baseline LPL activity and gene expression estimation. During a 4-year follow-up, 21 patients died due to tumor progression. One patient died due to a non- cancer reason and was not included in Cox regression analysis. High gene expression in the non- cancer lung tissue surrounding the tumor had no predictive value.

Our study further underlines the involvement of cancer tissue LPL activity in tumor progression. ATM activation in normal human tissues and testicular cancer. Cultured cells respond to genotoxic insults that induce DNA double-strand breaks by prompt activation of ATM through its autophosphorylation on serine Here we produced phospho-specific monoclonal antibodies against Sphosphorylated ATM pS-ATM , and applied them to immunohistochemical analyses of a wide range of normal human tissues and testicular tumors.

Our data show that regardless of proliferation and differentiation, most human tissues contain only the Snonphosphorylated, inactive form of ATM. In contrast, nuclear staining for pS-ATM was detected in subsets of bone-marrow lymphocytes and primary spermatocytes in the adult testes, cell types in which DSBs are generated during physiological V D J recombination and meiotic recombination, respectively. Among testicular germ-cell tumors, an aberrant constitutive pS-ATM was observed especially in embryonal carcinomas, less in seminomas, and only modestly in teratomas and the pre-invasive carcinoma-in-situ stage.

Collectively, our results strongly support the physiological relevance of the recently proposed model of ATM autoactivation, and provide further evidence for constitutive activation of the DNA damage machinery during cancer development. The new tools characterized here should facilitate monitoring of ATM activation in clinical specimens, and help develop future treatment strategies.

Cancerous 'floater': a lesson learned about tissue identity testing, endometrial cancer and microsatellite instability. A year-old woman presented with endometrial cells on a pap smear and underwent endometrial curettage. The specimen revealed secretory endometrium and a possible endometrial polyp.

In addition, a single 4 mm fragment of well-differentiated adenocarcinoma was found. Tissue identity DNA genotyping was performed and the adenocarcinoma tissue fragment showed a drastically different allelic pattern from that of the background endometrium.


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  4. To confirm tissue contamination, genotyping of three other tumor specimens-probable sources for a contaminant-was performed but failed to identify a match. Without confirmation of contamination, a second endometrial curettage was obtained from the patient, in which similar adenocarcinoma tissue was once again found.

    Further workup demonstrated that the patient had a microsatellite unstable MSI endometrial adenocarcinoma by immunohistochemistry and molecular testing. The patient subsequently underwent staging surgery, which revealed an early-stage, well-differentiated endometrioid adenocarcinoma.

    This case study illustrates an uncommon, yet important caveat of tissue identity testing by DNA genotyping, where MSI instability can significantly alter the allelic pattern of DNA polymorphisms in the tumor genome, leading to erroneous conclusion regarding the tissue identity. Awareness of this phenomenon is crucial for a molecular pathologist to avoid interpretation errors of tissue identity testing in a cancer diagnostic workup.

    Characterization of cancer and normal tissue fluorescence through wavelet transform and singular value decomposition. Gharekhan, Anita H. The statistical and characteristic features of the polarized fluorescence spectra from cancer , normal and benign human breast tissues are studied through wavelet transform and singular value decomposition. The discrete wavelets enabled one to isolate high and low frequency spectral fluctuations, which revealed substantial randomization in the cancerous tissues , not present in the normal cases.

    In particular, the fluctuations fitted well with a Gaussian distribution for the cancerous tissues in the perpendicular component. One finds non-Gaussian behavior for normal and benign tissues ' spectral variations. The study of the difference of intensities in parallel and perpendicular channels, which is free from the diffusive component, revealed weak fluorescence activity in the nm domain, for the cancerous tissues.

    This may be ascribable to porphyrin emission. The role of both scatterers and fluorophores in the observed minor intensity peak for the cancer case is experimentally confirmed through tissue -phantom experiments. Continuous Morlet wavelet also highlighted this domain for the cancerous tissue fluorescence spectra.

    Correlation in the spectral fluctuation is further studied in different tissue types through singular value decomposition. Apart from identifying different domains of spectral activity for diseased and non-diseased tissues , we found random matrix support for the spectral fluctuations. The small eigenvalues of the perpendicular polarized fluorescence spectra of cancerous tissues fitted remarkably well with random matrix prediction for Gaussian random variables, confirming our observations about spectral fluctuations in the wavelet domain.

    Expression profile of circular RNAs in human gastric cancer tissues. CircRNAs serve important roles in disease development and have the potential to serve as a novel class of biomarkers for clinical diagnosis. However, the role of circRNAs in the occurrence and development of gastric cancer GC remains unclear. In the present study, the expression profiles of circRNAs were compared between GC and adjacent normal tissues using a circRNA microarray, following which quantitative polymerase chain reaction qPCR was used to confirm the results of the circRNA microarray.

    A total of 10 circRNAs were selected for validation in three pairs of GC and adjacent noncancerous tissues. The qPCR results were consistent with the findings of the microarray-based expression analysis. Pathology tissue specimens with associated epidemiologic and clinical data are valuable for cancer research. Formalin-fixed paraffin-embedded tissue blocks were obtained from pathology laboratories on a loan basis for central processing of tissue microarrays, with additional free-standing tissue cores collected for nucleic acid extraction.

    The process of creating this resource was complex, involving multidisciplinary teams with expertise in pathology, epidemiology, information technology, project management, and specialized laboratories. Creating the PLCO tissue resource required a multistep process, including obtaining medical records and contacting pathology departments where pathology materials were stored after obtaining necessary patient consent and authorization. The potential to link tissue biomarkers to prospectively collected epidemiologic information, screening and clinical data, and matched blood or buccal samples offers valuable opportunities to study etiologic heterogeneity, mechanisms of carcinogenesis, and biomarkers for early detection and prognosis.

    The methods and protocols developed for this effort, and the detailed description of this resource provided here, will be useful for those seeking to use PLCO pathology tissue specimens for their research and may also inform future tissue collection efforts in other settings. Cancer Epidemiol Biomarkers Prev; 25 12 ; Optical redox imaging indices discriminate human breast cancer from normal tissues.

    Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer BC diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients.

    Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer -bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues p cancerous tissues p cancer with reasonable sensitivity and specificity.

    Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients. Characterizing viscoelastic properties of breast cancer tissue in a mouse model using indentation. Breast cancer is one of the leading cancer forms affecting females worldwide. Characterizing the mechanical properties of breast cancer tissue is important for diagnosis and uncovering the mechanobiology mechanism. Although most of the studies were based on human cancer tissue , an animal model is still describable for preclinical analysis.

    Using a custom-build indentation device, we measured the viscoelastic properties of breast cancer tissue from 4T1 and SKBR3 cell lines. A total of 7 samples were tested for each cancer tissue using a mouse model. We observed that a viscoelastic model with 2-term Prony series could best describe the ramp and stress relaxation of the tissue. In addition, by inspecting the cellular morphological structure of the two tissues , we found that SKBR3 tissues had a larger volume ratio of nuclei and a smaller volume ratio of extracellular matrix ECM.

    Compared with prior cellular mechanics studies, our results indicated that ECM could contribute to the stiffening the tissue -level behavior. The viscoelastic characterization of the breast cancer tissue contributed to the scarce animal model data and provided support for the linear viscoelastic model used for in vivo elastography studies. Results also supplied helpful information for modeling of the breast cancer tissue in the tissue and cellular levels.

    Creation of an optically tunable, solid tissue phantom for use in cancer detection. Tucker, Matthew B. An optically tunable, solid tissue phantom was developed in order to aid in the verification and validation of non-destructive cancer detection technologies based on fluorescence spectroscopy. The redox ratio of the solid phantoms were shown to be tunable; thus, indicating that these phantoms could be used to tailor specific optical conditions that mimic cancerous and healthy tissues.

    Therefore, this solid tissue phantom can serve as a suitable test bed to evaluate fluorescence spectroscopy based cancer detection devices. Adipose tissue and breast epithelial cells: a dangerous dynamic duo in breast cancer. Among the many different cell types surrounding breast cancer cells, the most abundant are those that compose mammary adipose tissue , mainly mature adipocytes and progenitors. New accumulating recent evidences bring the tumor-surrounding adipose tissue into the light as a key component of breast cancer progression.

    The purpose of this review is to emphasize the role that adipose tissue might play by locally affecting breast cancer cell behavior and subsequent clinical consequences arising from this dialog. Two particular clinical aspects are addressed: obesity that was identified as an independent negative prognostic factor in breast cancer and the oncological safety of autologous fat transfer used in reconstructive surgery for breast cancer patients. This is preceded by the overall description of adipose tissue composition and function with special emphasis on the specificity of adipose depots and the species differences, key experimental aspects that need to be taken in account when cancer is considered.

    Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue -specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. Breast cancer cell migration into tissues and toward tissue -conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay.

    Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment.

    Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. Published by Elsevier Inc. Why might people donate tissue for cancer research? While more research is necessary, a better understanding of the factors that motivate patients to give or refuse consent to tumour banking may ultimately improve consent practices, public trust and donation rates. Copyright S. Karger AG, Basel. Therefore, much effort is now directed toward developing alternative breast cancer detection technologies that exploit the Combining polarimetry and spectropolarimetry techniques in diagnostics of cancer changes in biological tissues.

    The aim of the study is combining polarimetry and spectropolarimetry techniques for identifying the changes of opticalgeometrical structure in different kinds of biotissues with solid tumours. It is researched that a linear dichroism appears in biotissues human esophagus, muscle tissue of rats, human prostate tissue , cervical smear with cancer diseases, magnitude of which depends on the type of the tissue and on the time of cancer process development.

    The crucial goal of kidney-sparing surgical resection of a malignant tumor is complete removal of the cancerous tissue. The exact border between the cancerous and normal tissues is not always possible to identify by naked eye, therefore, a supplementary intraoperative diagnosis is needed. Unfortunately, intraoperative pathology methods used nowadays are time consuming and of inadequate quality rendering not definitive diagnosis. It has recently been shown that ATR-FTIR spectroscopy can be used for fast discrimination between cancerous and normal kidney tissues by analyzing the collected spectra of the tissue touch imprint smears.

    Most prominent differences are obtained in the wavenumber region from cm-1 to cm-1, where the spectral bands due to the molecular vibrations of glycogen arise in the spectra of cancerous tissue smears. Such method of detection of cancerous tissue is limited by requirement to transfer the suspected tissue from the body to the FTIR instrument and stamp it on an ATR crystal of the spectrometer. We propose a spectroscopic tool which exploits the same principle of detection of cancerous cells as mentioned above, but does not require the tissue to be transferred from the body to the spectrometer.

    The portable spectrometer used in this design is equipped with fiber ATR probe and a sensitive liquid nitrogen cooled MCT detector. The design of the fiber probe allows the ATR tip to be changed easily in order to use only new sterilized tips for each measurement point of the tissue. It also enables sampling multiple areas of the suspected tissue with high lateral resolution which, in turn, increases accuracy with which the marginal regions between normal and cancerous tissues can be identified. Due to the loss of optical signal in the fiber probe the spectra have lower signal-to-noise ratio than in the case of standard ATR sampling setup.

    However, software for the spectral analysis used with the fiber probe design is still able to distinguish. Archived human tissues are an essential resource for translational research. Formalin-fixed, paraffin embedded FFPE tissues from cancer patients are used in a wide range of assays, including RT-PCR, SNP profiling, multiplex biomarkers, imaging biomarkers, targeted exome, whole exome, and whole genome sequencing.

    Scattering properties of normal and cancerous tissues from human stomach based on phase-contrast microscope. In order to study scattering properties of normal and cancerous tissues from human stomach, we collect images for human gastric specimens by using phase-contrast microscope. The images were processed by the way of mathematics morphology. The equivalent particle size distribution of tissues can be obtained. Combining with Mie scattering theory, the scattering properties of tissues can be calculated.

    Assume scattering of light in biological tissue can be seen as separate scattering events by different particles, total scattering properties can be equivalent to as scattering sum of particles with different diameters. The results suggest that scattering coefficient of the cancerous tissue is significantly higher than that of normal tissue. The scattering phase function is different especially in the backscattering area.

    Those are significant clinical benefits to diagnosis cancerous tissue. Venables, Julian P. Alternative splicing provides a critical and flexible layer of regulation intervening in many biological processes to regulate the diversity of proteins and impact cell phenotype. To identify alternative splicing differences that distinguish epithelial from mesenchymal tissues , we have investigated hundreds of cassette exons using a high-throughput reverse transcription-PCR RT-PCR platform. Extensive changes in splicing were noted between epithelial and mesenchymal tissues in both human colon and ovarian tissues , with many changes from mostly one splice variant to predominantly the other.

    Remarkably, many of the splicing differences that distinguish normal mesenchymal from normal epithelial tissues matched those that differentiate normal ovarian tissues from ovarian cancer. By knocking down 78 potential splicing factors in five cell lines, we provide an extensive view of the complex regulatory landscape associated with the epithelial and mesenchymal states, thus revealing that RBFOX2 is an important driver of mesenchymal tissue -specific splicing.

    Multispectral fluorescence imaging of human ovarian and Fallopian tube tissue for early stage cancer detection. Cancer changes molecular concentrations of various endogenous fluorophores. Using specific excitation wavelengths and emissions bands on a Multispectral Fluorescence Imaging MFI system, spatial and spectral data over a wide field of view can be collected from endogenous fluorophores.

    Wavelength specific reflectance images provide additional information to normalize for tissue geometry and blood absorption.

    Ratiometric combination of the images may create high contrast between neighboring normal and abnormal tissue. Twenty-six women undergoing oophorectomy or debulking surgery consented the use of surgical discard tissue samples for MFI imaging. Forty-nine pieces of ovarian tissue and thirty-two pieces of Fallopian tube tissue were collected and imaged with excitation wavelengths between nm and nm.

    After imaging, each tissue sample was fixed, sectioned and HE stained for pathological evaluation. Comparison of mean intensity values between normal, benign, and cancerous tissue demonstrate a general trend of increased fluorescence of benign tissue and decreased fluorescence of cancerous tissue when compared to normal tissue. The predictive capabilities of the mean intensity measurements are tested using multinomial logistic regression and quadratic discriminant analysis. Adaption of the system for in vivo Fallopian tube and ovary endoscopic imaging is possible and is briefly described.

    We first analysed The Cancer Genome Natl Acad. USA 96, — Singh, S. Characterization of sequences in human Raman microspectroscopy of Hematoporphyrins. Imaging of the noncancerous and the cancerous human breast tissues with photosensitizers. Raman microspectroscopy combined with fluorescence were used to study the distribution of Hematoporphyrin Hp in noncancerous and cancerous breast tissues. The results demonstrate the ability of Raman spectroscopy to distinguish between noncancerous and cancerous human breast tissue and to identify differences in the distribution and photodegradation of Hematoporphyrin, which is a photosensitizer in photodynamic therapy PDT , photodynamic diagnosis PDD and photoimmunotherapy PIT of cancer.

    Presented results show that Hematoporphyrin level in the noncancerous breast tissue is lower compared to the cancerous one. We have proved also that the Raman intensity of lipids and proteins doesn't change dramatically after laser light irradiation, which indicates that the PDT treatment destroys preferably cancer cells, in which the photosensitizer is accumulated. The specific subcellular localization of photosensitizer for breast tissues samples soaked with Hematoporphyrin was not observed. Trace elemental analysis in cancer -afflicted tissues of penis and testis by PIXE technique.

    Naga Raju, G. PIXE technique was employed to estimate the trace elemental concentrations in the biological samples of cancerous penis and testis. A 3 MeV proton beam was employed to excite the samples. From the present results it can be seen that the concentrations of Cl, Fe and Co are lower in the cancerous tissue of the penis when compared with those in normal tissue while the concentrations of Cu, Zn and As are relatively higher.

    In the cancerous tissue of testis, the concentrations of K, Cr and Cu are higher while the concentrations of Fe, Co and Zn are lower when compared to those in normal tissue of testis. The concentrations of Cl, Ca, Ti and Mn are in agreement in both cancerous and normal tissues of testis. The higher levels of Cu lead to the development of tumor. Our results also support the underlying hypothesis of an anticopper, antiangiogenic approach to cancer therapy.

    Lead, selenium and nickel concentrations in epithelial ovarian cancer , borderline ovarian tumor and healthy ovarian tissues. Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer , but scant data is available for ovarian cancer.

    Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer , borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer , 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries.

    Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues , borderline papillary projections and capsular tissue samples were not different.

    Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before.

    Evidence that breast tissue stiffness is associated with risk of breast cancer. Evidence from animal models shows that tissue stiffness increases the invasion and progression of cancers , including mammary cancer. We here use measurements of the volume and the projected area of the compressed breast during mammography to derive estimates of breast tissue stiffness and examine the relationship of stiffness to risk of breast cancer.

    Mammograms were used to measure the volume and projected areas of total and radiologically dense breast tissue in the unaffected breasts of women with newly diagnosed breast cancer cases and women of the same age who did not have breast cancer controls. Measures of breast tissue volume and the projected area of the compressed breast during mammography were used to calculate the deformation of the breast during compression and, with the recorded compression force, to estimate the stiffness of breast tissue.

    Stiffness was compared in cases and controls, and associations with breast cancer risk examined after adjustment for other risk factors. An estimate of breast tissue stiffness was associated with breast cancer risk and improved risk prediction based on mammographic measures and other risk factors. Stiffness may provide an additional mechanism by which breast tissue composition is associated with risk of breast cancer and merits examination using more direct methods of measurement. Boyd, Norman F.

    Background Evidence from animal models shows that tissue stiffness increases the invasion and progression of cancers , including mammary cancer. Methods Mammograms were used to measure the volume and projected areas of total and radiologically dense breast tissue in the unaffected breasts of women with newly diagnosed breast cancer cases and women of the same age who did not have breast cancer controls.

    Droits d'auteur :

    Conclusion An estimate of breast tissue stiffness was associated with breast cancer risk and improved risk prediction based on mammographic measures and other risk factors. The magnitude of linear dichroism of biological tissues as a result of cancer changes. Bojchuk, T.

    The results of studies of linear dichroism values of different types of biological tissues human prostate, esophageal epithelial human muscle tissue in rats both healthy and infected tumor at different stages of development are shown here. It is researched that in all cases in biological tissues prostate gland, esophagus, human muscle tissue in rats with cancer the linear dichroism arises, the value of which depends on the type of tissue and time of the tumor process.

    As for healthy tissues linear dichroism is absent, the results may have diagnostic value for detecting and assessing the degree of development of cancer. Background Rectal cancer is one of the most prevalent tumor types. Understanding the metabolic profile of rectal cancer is important for developing therapeutic approaches and molecular diagnosis. A total of 38 differential metabolites were identified, 16 of which were closely correlated with the stage of rectal cancer. The up-regulation of 10 metabolites, including lactate, threonine, acetate, glutathione, uracil, succinate, serine, formate, lysine and tyrosine, were detected in the cancer tissues.

    On the other hand, 6 metabolites, including myo-inositol, taurine, phosphocreatine, creatine, betaine and dimethylglycine were decreased in cancer tissues. These modified metabolites revealed disturbance of energy, amino acids, ketone body and choline metabolism, which may be correlated with the progression of human rectal cancer. Conclusion Our findings firstly identify the distinguishing metabolites in different stages of rectal cancer tissues , indicating possibility of the attribution of metabolites disturbance to the progression of rectal cancer.

    The altered metabolites may be as potential biomarkers, which would. The nanomechanical signature of liver cancer tissues and its molecular origin. Patients with cirrhosis are at higher risk of developing hepatocellular carcinoma HCC , the second most frequent cause of cancer -related deaths. Here, we show that the nanomechanical signature of liver tissue is directly correlated with the development of HCC.

    Using indentation-type atomic force microscopy IT-AFM , we demonstrate that the lowest elasticity peak LEP in the Young's modulus distribution of surgically removed liver cancer tissues can serve as a mechanical fingerprint to evaluate the malignancy of liver cancer.

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    Cirrhotic tissues shared the same LEP as normal tissues. However, a noticeable downward shift in the LEP was detected when the cirrhotic tissues progressed to a malignant state, making the tumor tissues more prone to microvascular invasion. Cell-level mechanistic studies revealed that the expression level of a Rho-family effector mDia1 was consistent with the mechanical trend exhibited by the tissue.

    Our findings indicate that the mechanical profiles of liver cancer tissues directly varied with tumor progression, providing an additional platform for the future diagnosis of HCC. Cancer testis antigen OY-TES analysis of protein expression in ovarian cancer with tissue microarrays. Revised manuscript accepted for publication March 5, Objectives: The purpose of this study was to determine the potential of cancer testis antigen OY-TES-1 as a vaccine for ovarian cancer OC.

    OC adjacent tissues only demonstrated lower immunostaining intensity, whereas some of OC tissues presented higher immunostaining intensity and majority showed the heterogeneity of protein distribution. There was no statistically significant correlation found between OY-TES-1 expression and any other clinicopathological traits such as age, FIGO stage, pathological grade, and histological type.

    Breast cancer is the largest detected cancer amongst women in the US. In this work, our team reports on the development of piezoresistive microcantilevers PMCs to investigate their potential use in the accurate detection and characterization of benign and diseased breast tissues by performing indentations on the micro-scale tissue specimens. The PMCs used in these experiments have been fabricated using laboratory-made silicon-on-insulator SOI substrate, which significantly reduces the fabrication costs. Breast tissue cores from seven different specimens were indented using PMC to identify benign and cancerous tissue cores.

    Furthermore, field emission scanning electron microscopy FE-SEM of benign and cancerous specimens showed marked differences in the tissue morphology, which further validates our observed experimental data with the PMCs. While these patient aspecific feasibility studies clearly demonstrate the ability to discriminate between benign and cancerous breast tissues , further investigation is necessary to perform automated mechano-phenotyping classification of breast cancer : from onset to disease progression.

    Identification of tumor cells infiltrating into connective tissue in esophageal cancer by multiphoton microscopy. Esophageal cancer is one of the most common malignancies of the gastrointestinal cancers and carries poorer prognosis than other gastrointestinal cancers.

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    In general practice, the depth of tumor infiltration in esophageal wall is crucial to establishing appropriate treatment plan which is established by detecting the tumor infiltration depth. Connective tissue is one of the main structures that form the esophageal wall. So, identification of tumor cells infiltrating into connective tissue is helping for detecting the tumor infiltration depth. Our aim is to evaluate whether multiphoton microscopy MPM can be used to detect tumor cells infiltrating into connective tissue in the esophageal cancer.

    MPM is well-suited for real-time detecting morphologic and cellular changes in fresh tissues since many endogenous fluorophores of fresh tissues are excited through two-photon excited fluorescence TPEF and second harmonic generation SHG. In this work, microstructure of tumor cells and connective tissue are first studied. Then, morphological changes of collagen fibers after the infiltration of tumor cells are shown. These results show that MPM has the ability to detect tumor cells infiltrating into connective tissue in the esophageal cancer.

    In the future, MPM may be a promising imaging technique for detecting tumor cells in esophageal cancer. This research aims to validate a new biomarker of breast cancer by introducing electromechanical coupling factor of breast tissue samples as a possible additional indicator of breast cancer. Since collagen fibril exhibits a structural organization that gives rise to a piezoelectric effect, the difference in collagen density between normal and cancerous tissue can be captured by identifying the corresponding electromechanical coupling factor. The design of a portable diagnostic tool and a microelectromechanical systems MEMS -based biochip, which is integrated with a piezoresistive sensing layer for measuring the reaction force as well as a microheater for temperature control, is introduced.

    To verify that electromechanical coupling factor can be used as a biomarker for breast cancer , the piezoelectric model for breast tissue is described with preliminary experimental results on five sets of normal and invasive ductal carcinoma IDC samples in the temperature range. While the stiffness of breast tissues can be captured as a representative mechanical signature which allows one to discriminate among tissue types especially in the higher strain region, the electromechanical coupling factor shows more distinct differences between the normal and IDC groups over the entire strain region than the mechanical signature.

    From the two-sample -test, the electromechanical coupling factor under compression shows statistically significant differences 0. The increase in collagen density in breast tissue is an objective and reproducible characteristic of breast cancer. Although characterization of mechanical tissue property has been shown to be useful for differentiating cancerous tissue from normal tissue , using a single parameter may not be sufficient for practical usage due to inherent variation among biological samples. The portable breast cancer diagnostic tool reported in this manuscript shows the feasibility of measuring multiple.

    This book comprehensively covers modern soft tissue pathology and includes both tumors and non-neoplastic entities. Soft tissues make up a large bulk of the human body, and they are susceptible to a wide range of diseases.


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